The mechanism and significance of Evf ncRNA regulation of the DLX genes

This grant investigates a new mechanism of gene regulation that is critical for GABAergic interneuron development. Since altered GABAergic interneuron function has been linked to epilepsy, autism, schizophrenia, and mental retardation, studies on the normal development of GABAergic interneurons are critical to understanding the molecular bases for these diseases. There are two specific goals of this project. The first is to gain a better understanding of a novel mechansim of RNA dependent transcriptional regulation. The second is to gain a better understanding of how GABAergic neuronal differentiation and migration are controlled. The first goal focuses on how the novel non-coding RNAs, embryonic ventral forebrain (Evf), influence transcription of the Dlx 5/6 enhancer. The proposed studies would be the first to investigate the in vivo role of developmentally regulated ncRNA-dependent modulation of enhancer activity. The importance of mechanistic studies of RNA function is clear from the number of regulatory RNAs thought to be involved different diseases. These include: Prader Willi Syndrome, diGeorge Syndrome, Beckwith-Wiedeman syndrome, Spinocerebellar ataxia type 8, and campomelic dysplasia. Ultimately, it is hoped that a better understanding of the development of specific neuronal subpopulations in the brain will lead to the prevention and treatment of human neurological diseases.